Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin.

This study demonstrates the effect of substrate's geometrical cues on viability and the efficacy of an anti-cancer drug, doxorubicin (DOX), on breast cancer cells. It is hypothesized that the surface topographical properties can mediate the cellular drug intake. Pseudo-three dimensional (3D) platforms were fabricated using imprinting technique from polydimethylsiloxane (PDMS) and gelatin methacryloyl (GelMA) hydrogel to recapitulate topography of cells' membranes. The cells exhibited higher viability on the cell-imprinted platforms for both PDMS and GelMA materials compared to the plain/flat counterparts. For instance, MCF7 cells showed a higher metabolic activity (11.9%) on MCF7-imprinted PDMS substrate than plain PDMS. The increased metabolic activity for the imprinted GelMA was about 44.2% compared to plain hydrogel. The DOX response of cells was monitored for 24 h. Although imprinted substrates demonstrated enhanced biocompatibility, the cultured cells were more susceptible to the drug compared to the plain substrates. In particular, MCF7 cells on imprinted PDMS and GelMA substrates showed 37% and 50% higher in cell death compared to the corresponding plain PDMS and GelMA, respectively. Interestingly, the drug susceptibility of the cells on the imprinted hydrogel was about 70% higher than the cells cultured on imprinted PDMS substrates. Having MCF7 cell-imprinted substrates, DOX responses of two other breast cancer cell lines, SKBR3 and ZR-75-1, were also evaluated. The results support that cell membrane curvature developed by multiscale topography is able to mediate intracellular signaling and drug intake. STATEMENT OF SIGNIFICANCE: Research in biological sciences and drug discovery mostly rely on two dimensional (2D) cell culture techniques which cannot provide a reliable physiologically relevant environment. Lack of extracellular matrix and a large shift in physicochemical properties of conventional 2D substrates can induce aberrant cellular behaviors. While chemical composition, topographical, and mechanical properties of substrates have remarkable impacts on drug susceptibility, gene expression, and protein synthesis, the most cell culture plates are from rigid and plain substrates. A number of (bio)polymeric 3D-platforms have been introduced to resemble innate cell microenvironment. However, their intricate culture protocols restrain their applications in demanding high-throughput drug screening. To address the above concerns, in the present study, a hydrogel-based pseudo-3D substrate with imprinted cell features has been introduced.

A Mathematical Model for Vibration Behavior Analysis of DNA and Using a Resonant Frequency of DNA for Genome Engineering.

The DNA molecule is the most evolved and most complex molecule created by nature. The primary role of DNA in medicine is long-term storage of genetic information. Genetic modifying is one of the most critical challenges that scientists face. On the other hand, it is said that under the influence of acoustic, electromagnetic, and scalar waves, the genetic code of DNA can be read or rewritten. In this article, the most accurate and comprehensive dynamic model will be presented for DNA. Each of the two strands is modeled with an out of plane curved beam and then by doubling this two strands with springs, consider the hydrogen bond strength between this two strands. Beams are traditionally descriptions of mechanical engineering structural elements or building. However, any structure such as automotive automobile frames, aircraft components, machine frames, and other mechanical or structural systems contain beam structures that are designed to carry lateral loads are analyzed similarly. Also, in this model, the mass of the nucleobases in the DNA structure, the effects of the fluid surrounding the DNA (nucleoplasm) and the effects of temperature changes are also considered. Finally, by deriving governing equations from Hamilton's principle method and solving these equations with the generalized differential quadrature method (GDQM), the frequency and mode shape of the DNA is obtained for the first time. In the end, validation of the obtained results from solving the governing equations of mathematical model compared to the obtained results from the COMSOL software is confirmed. By the help of these results, a conceptual idea for controlling cancer with using the DNA resonance frequency is presented. This idea will be presented to stop the cancerous cell's protein synthesis and modifying DNA sequence and genetic manipulation of the cell. On the other hand, by the presented DNA model and by obtaining DNA frequency, experimental studies of the effects of waves on DNA such as phantom effect or DNA teleportation can also be studied scientifically and precisely.

Influence of various setting angles on vibration behavior of rotating graphene sheet: continuum modeling and molecular dynamics simulation.

The Eringen's nonlocal elasticity theory is employed to examine the free vibration of a rotating cantilever single-layer graphene sheet (SLGS) under low and high temperature conditions. The governing equations of motion and the related boundary conditions are obtained through Hamilton's principle based on the first-order shear deformation theory (FSDT) of nanoplates. The generalized differential quadrature method (GDQM) is utilized to solve the nondimensional equations of motion. The molecular dynamics (MD) simulation is conducted, and fundamental frequencies of the rotating cantilever square SLGS are computed using the fast Fourier transform (FFT). The comparison of MD and GDQM results leads to finding the appropriate value of the nonlocal parameter for the first time. As an interesting result, this value of the nonlocal parameter is independent of the angular velocity. Results indicate that increases in various parameters, such as the angular velocity, hub radius, nonlocal parameter, and temperature changes in low temperature conditions, leads the first and the second frequencies to increase. In addition, it can be seen that the influence of the hub radius or nonlocal parameters on frequencies cannot be ignored in high angular velocities. Moreover, it is not possible to neglect the angular velocity or nonlocal parameter in high hub radius. The results show that the influence of parameters such as setting angle or nonlocal parameter on the first and the second frequencies increases when some parameters increase, such as the angular velocity, hub radius or temperature change. Graphical abstract (a) A schematic of a rotating cantilever nanoplate. (b) A schematic of cantilever armchair SLGS simulated by MD.